Gualou Guizhi decoction promotes therapeutic angiogenesis via the miR210/HIF/VEGF pathway in vivo and in vitro.
Pharm Biol
; 61(1): 779-789, 2023 Dec.
Article
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| MEDLINE
| ID: mdl-37158290
ABSTRACT
CONTEXT Gualou Guizhi decoction (GLGZD) is an ancient Chinese classical prescription widely used to treat ischemic stroke. However, the molecular mechanisms of GLGZD promoting angiogenesis are unavailable. OBJECTIVE:
This study investigates the angiogenesis effect of GLGZD as well as its mechanism. MATERIALS ANDMETHODS:
Ischemic stroke was established by middle cerebral artery occlusion/reperfusion (MCAO/R) in male Sprague-Dawley (SD) rats. The GLGZD groups received GLGZD (3.6, 7.2 and 14.4 g/kg) orally. Oxygen-glucose deprivation/reoxygenation (OGD/R) model was constructed in HUVECs receiving GLGZD medicated serum (MS). MRI, H&E staining, qRT-PCR, western blot and immunofluorescence methods were employed. miRNA210 inhibitor was employed to confirm the effects of GLGZD on promoting angiogenesis. Dual luciferase assay was used to verify the binding of miRNA210 with HIF mRNA.RESULTS:
GLGZD treatment improved neurological function (by 27%), alleviated neuronal injury (by 76%), reduced infarct volume (by 74%) and increased microvessel density (by fourfold) in vivo. In vitro data had also shown that GLGZD caused proliferation of the cells (by 58%), their migration, and eventual formation of tubes (by threefold). Simultaneously, GLGZD enhanced the levels of angiogenesis-related molecules and activated the HIF/VEGF signalling pathway. Surprisingly, the beneficial effects of GLGZD on post-stroke angiogenesis and neurological recovery were weakened by miRNA210 inhibitor, and also abolished the mediation of proangiogenic factors. miRNA210 directly targeted HIF mRNA. DISCUSSION ANDCONCLUSIONS:
GLGZD enhances angiogenesis via activation of the miRNA210/HIF/VEGF signalling pathway, suggesting it can be a novel application as an effective angiogenic formula for stroke recovery.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Isquemia Encefálica
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Accidente Cerebrovascular
/
MicroARNs
/
Accidente Cerebrovascular Isquémico
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Pharm Biol
Año:
2023
Tipo del documento:
Article